Small-animal PET scanners have not reached the highest sensitivity and spatial resolution that is achievable, largely due to an unfavorable trade-off between spatial resolution and efficiency in most detector designs. The objective of this proposal is to develop high resolution, high sensitivity depth-encoding detectors for in vivo molecular imaging with PET based on position-sensitive avalanche photodiode (PSAPD) technology and develop a high spatial resolution and high resolution uniformity prototype scanner for small-animal imaging based on PSAPD/LSO detector modules. PSAPDs offer several attractive features including low density readout (event location is encoded in just four signal outputs), thin cross-section (enabling dual- ended read out of scintillator arrays to provide depth of interaction information) and high quantum efficiency. Preliminary data has clearly demonstrated the ability of these devices to resolve arrays of 1x1 mm cross- section LSO crystals and to provide a 3-4 mm depth of interaction resolution with 20 mm thick detectors. The research in this proposal seeks to develop and optimize PSAPD detectors suitable for incorporation into a high resolution, high sensitivity small-animal PET scanner. Specifically, experiments will address the minimum resolvable LSO crystal size as a function of PSAPD surface area and temperature, the effect of different PSAPD read out schemes, depth of interaction resolution as a function of crystal length, size, and surface treatment, and the stability of PSAPD as a function of time, bias voltage and temperature. A complete evaluation of PSAPD/LSO PET detectors will include measurements of flood histograms, individual crystal energy spectra, depth of interaction resolution, timing resolution and intrinsic spatial resolution. Quantitative comparison will be made to LSO detectors based on position sensitive photomultiplier tubes . (the technology currently used in most small-animal PET systems). Finally a simple single detector ring small-animal PET scanner will be developed using the optimized PSAPD/LSO detectors as a proof of concept. Electronics, data acquisition and image reconstruction algorithms will be developed for the PET system with depth of interaction capability. Based on these results, the performance (in terms of spatial resolution and sensitivity) of a multi-ring small-animal PET system built from these detector modules will be predicted and compared with available commercial small-animal PET scanners.